The double exposure
caused damage to brain regions known to play a role in learning and
memory, the team reported in the March 2004 issue of Toxicology and
Applied Pharmacology. The result might therefore help to explain earlier
suggestions that children whose mothers are administered terbutaline
suffer cognitive deficits. The National Institutes of Health supported
the research.

Premature labor
occurs in approximately 20 percent of all pregnancies in the United
States. Of those, an estimated 1 million women annually are treated
with terbutaline or related drugs to halt the early contractions. The
drugs administered to pregnant women also penetrate to the fetus where
they affect brain development.

The work highlights
the synergistic and unpredictable effects that exposure to multiple
chemicals can have on the brain, said senior author of the study Theodore
Slotkin, Ph.D., professor of pharmacology and cancer biology at Duke.
Moreover, just as some gene variants confer heightened disease risk,
the study suggests that certain early drug or chemical exposures can
predispose people to particular ailments, he added.

"The adverse
effects of sequential exposure to the two compounds on certain brain
characteristics were more than the sum of the two agents' independent
effects," Slotkin said. "Our findings suggest that exposure
to drugs like terbutaline early in development can leave individuals
set on a hair trigger for further problems when subsequently faced with
environmental chemicals."

Sensitive subgroups
should be taken into consideration when determining safe levels of the
chemicals in the household and the environment, Slotkin said.

Chlorpyrifos was
one of the most commonly used insecticides in the United States for
both agriculture and household uses prior to the year 2000 when the
EPA began restricting the chemical from home use in stages. However,
chlorpyrifos is still used for mosquito control of the West Nile virus
and is widely used for agricultural purposes.

The highest exposures to environmental contaminants, including chlorpyrifos,
occur in young children due to the fact that they crawl across the ground
and other surfaces and put objects in their mouths, Slotkin said. Children
also consume a greater volume of food and water -- often containing
pesticides -- relative to their body weight compared to adults. Studies
of chlorpyrifos levels in school-age children have found that virtually
everyone is exposed, he said.

The researchers
administered terbutaline alone, chlorpyrifos alone or terbutaline followed
by chlorpyrifos to three groups of young rats. Rats received terbutaline
at 2 to 4 days old, a time equivalent to the early third trimester of
human development. Chlorpyrifos was administered at day 11 to 14. A
fourth untreated group served as a control.

Both chemicals independently
caused brain injuries not seen in the control rats, including the loss
of brain cells and the nerve cell projections critical to communication
among neurons. The effects persisted into adulthood.

The combined chemical
treatment further aggravated the chemicals' damaging effects on the
brain, the team reported. The brains of rats exposed to both chemicals
also showed reduced nerve cell activity that the researchers did not
observe in rats exposed to either chemical alone. Furthermore, portions
of the brain central to learning and memory, including the hippocampus,
suffered significant loss of brain cells and nerve cell projections
in rats exposed to both chemicals. Rats administered either chemical
alone showed much smaller effects on these regions, the researchers
said.

"It is increasingly
clear that environmental toxicants target specific human subpopulations,"
said Slotkin. "This study suggests that early drug or chemical
exposures might underlie some of these differences in susceptibility.
We need to start looking for such vulnerable groups and considering
them when making decisions about legislation. It is not adequate to
set the allowable concentrations for certain chemicals at levels that
might be unsafe for large segments of the population."

TAKE ACTION:
Protect your and your children's health by avoiding hazardous
pesticides such as chlorpyrifos. To find a pest control company that
provides least hazardous pest management, see Beyond Pesticides' Safety
Source.

Also, contact Mr.
Michael Leavitt, EPA Administrator, by email,
phone: 202-564-4711, or fax: 202-501-1470, and urge EPA to ban all uses
of chlorpyrifos (such as for public health and agricultural uses). Demand
that the agency immediately require toxicity data to include the cumulative
effects or synergistic interactions with other pesticides, pollutants
and pharmaceuticals.